CA2577922C - Compose de phosphoramidite et procede de fabrication d'oligo-arn - Google Patents

Compose de phosphoramidite et procede de fabrication d'oligo-arn Download PDF

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Publication number: CA2577922C
Authority: CA; Canada
Prior art keywords: compound; general formula; following general; same; reaction
Prior art date: 2004-08-26
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA2577922A

Other languages

English (en)

Other versions

CA2577922A1 (fr

Inventor

Tadaaki Ohgi

Kouichi Ishiyama

Yutaka Masutomi

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Nippon Shinyaku Co Ltd

Original Assignee

Nippon Shinyaku Co Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2004-08-26

Filing date

2005-08-25

Publication date

2013-06-25

2005-08-25 Application filed by Nippon Shinyaku Co Ltd filed Critical Nippon Shinyaku Co Ltd

2006-03-02 Publication of CA2577922A1 publication Critical patent/CA2577922A1/fr

2013-06-25 Application granted granted Critical

2013-06-25 Publication of CA2577922C publication Critical patent/CA2577922C/fr

2025-08-25 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

-1 Phosphoramidite compound Chemical class 0.000 title claims abstract description 106
238000004519 manufacturing process Methods 0.000 title claims description 35
125000006239 protecting group Chemical group 0.000 claims abstract description 41
125000001424 substituent group Chemical group 0.000 claims abstract description 40
125000000217 alkyl group Chemical group 0.000 claims abstract description 30
125000003545 alkoxy group Chemical group 0.000 claims abstract description 22
229910052717 sulfur Inorganic materials 0.000 claims abstract description 13
125000004434 sulfur atom Chemical group 0.000 claims abstract description 13
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 12
125000004122 cyclic group Chemical group 0.000 claims abstract description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
239000001257 hydrogen Substances 0.000 claims abstract description 6
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract description 3
239000001301 oxygen Substances 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 216
238000000034 method Methods 0.000 claims description 64
NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 claims description 38
239000000203 mixture Substances 0.000 claims description 38
239000003795 chemical substances by application Substances 0.000 claims description 33
229910052736 halogen Inorganic materials 0.000 claims description 33
150000002367 halogens Chemical class 0.000 claims description 33
239000002253 acid Substances 0.000 claims description 25
239000007787 solid Substances 0.000 claims description 25
108020004707 nucleic acids Proteins 0.000 claims description 22
102000039446 nucleic acids Human genes 0.000 claims description 22
150000007523 nucleic acids Chemical class 0.000 claims description 22
125000004093 cyano group Chemical group *C#N 0.000 claims description 21
MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 claims description 19
NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 claims description 19
229940029575 guanosine Drugs 0.000 claims description 19
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 16
UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 16
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
229920002477 rna polymer Polymers 0.000 claims description 16
239000000178 monomer Substances 0.000 claims description 15
239000007800 oxidant agent Substances 0.000 claims description 13
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 12
230000003213 activating effect Effects 0.000 claims description 11
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 10
125000004423 acyloxy group Chemical group 0.000 claims description 9
150000003573 thiols Chemical class 0.000 claims description 9
229930024421 Adenine Natural products 0.000 claims description 8
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 8
125000002252 acyl group Chemical group 0.000 claims description 8
229960000643 adenine Drugs 0.000 claims description 8
229940104302 cytosine Drugs 0.000 claims description 8
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 8
150000003973 alkyl amines Chemical class 0.000 claims description 5
229940113082 thymine Drugs 0.000 claims description 5
229940035893 uracil Drugs 0.000 claims description 5
108091027075 5S-rRNA precursor Proteins 0.000 claims description 4
150000001409 amidines Chemical class 0.000 claims description 3
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical group [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims description 3
HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 3
XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 2
HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 claims 1
HAOXPVKBQMNHRW-ISZBJVJQSA-N C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)OC[C@@H]1[C@@H](OP(O)(CCC#N)N(C(C)C)C(C)C)[C@@H](OCOCCC#N)[C@H](N2C(N=C(NC(C)=O)C=C2)=O)O1 Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)OC[C@@H]1[C@@H](OP(O)(CCC#N)N(C(C)C)C(C)C)[C@@H](OCOCCC#N)[C@H](N2C(N=C(NC(C)=O)C=C2)=O)O1 HAOXPVKBQMNHRW-ISZBJVJQSA-N 0.000 claims 1
VBCWSVTZRWHKGV-KVGMPSGPSA-N C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)OC[C@@H]1[C@@H](OP(O)(CCC#N)N(C(C)C)C(C)C)[C@@H](OCOCCC#N)[C@H](N2C(NC(=O)C=C2)=O)O1 Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)OC[C@@H]1[C@@H](OP(O)(CCC#N)N(C(C)C)C(C)C)[C@@H](OCOCCC#N)[C@H](N2C(NC(=O)C=C2)=O)O1 VBCWSVTZRWHKGV-KVGMPSGPSA-N 0.000 claims 1
MENGCNUGGJOQCT-FOQJVDBMSA-N C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)OC[C@@H]1[C@@H](OP(O)(CCC#N)N(C(C)C)C(C)C)[C@@H](OCOCCC#N)[C@H](N2C3=C(C(NC(NC(C)=O)=N3)=O)N=C2)O1 Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)OC[C@@H]1[C@@H](OP(O)(CCC#N)N(C(C)C)C(C)C)[C@@H](OCOCCC#N)[C@H](N2C3=C(C(NC(NC(C)=O)=N3)=O)N=C2)O1 MENGCNUGGJOQCT-FOQJVDBMSA-N 0.000 claims 1
YXGIXZCIPKFUCS-WTZZGMGRSA-N C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)OC[C@@H]1[C@@H](OP(O)(CCC#N)N(C(C)C)C(C)C)[C@@H](OCOCCC#N)[C@H](N2C3=NC=NC(NC(C)=O)=C3N=C2)O1 Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)OC[C@@H]1[C@@H](OP(O)(CCC#N)N(C(C)C)C(C)C)[C@@H](OCOCCC#N)[C@H](N2C3=NC=NC(NC(C)=O)=C3N=C2)O1 YXGIXZCIPKFUCS-WTZZGMGRSA-N 0.000 claims 1
230000015572 biosynthetic process Effects 0.000 abstract description 9
238000003786 synthesis reaction Methods 0.000 abstract description 9
125000006575 electron-withdrawing group Chemical group 0.000 abstract description 3
238000006243 chemical reaction Methods 0.000 description 166
239000000243 solution Substances 0.000 description 102
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
239000003153 chemical reaction reagent Substances 0.000 description 54
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
239000002904 solvent Substances 0.000 description 46
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 39
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 32
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 30
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
238000010898 silica gel chromatography Methods 0.000 description 26
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 25
230000002152 alkylating effect Effects 0.000 description 25
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
230000035484 reaction time Effects 0.000 description 21
229940045145 uridine Drugs 0.000 description 20
125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 19
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
239000002126 C01EB10 - Adenosine Substances 0.000 description 17
229960005305 adenosine Drugs 0.000 description 17
239000002585 base Substances 0.000 description 17
238000005160 1H NMR spectroscopy Methods 0.000 description 16
DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 16
239000002994 raw material Substances 0.000 description 16
DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 14
UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 14
125000003118 aryl group Chemical group 0.000 description 14
UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 14
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 14
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 14
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 13
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
230000002140 halogenating effect Effects 0.000 description 13
150000003833 nucleoside derivatives Chemical class 0.000 description 13
101150041968 CDC13 gene Proteins 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 9
BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 8
NXXJKXHLERAGKZ-UHFFFAOYSA-N 3-chloro-2-[(3-chloro-2-cyanopropoxy)methyl]propanenitrile Chemical compound ClCC(C#N)COCC(CCl)C#N NXXJKXHLERAGKZ-UHFFFAOYSA-N 0.000 description 8
238000000605 extraction Methods 0.000 description 8
239000002808 molecular sieve Substances 0.000 description 8
230000007935 neutral effect Effects 0.000 description 8
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 7
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 7
239000012300 argon atmosphere Substances 0.000 description 7
125000003710 aryl alkyl group Chemical group 0.000 description 7
238000004440 column chromatography Methods 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
239000011734 sodium Substances 0.000 description 7
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
150000008065 acid anhydrides Chemical class 0.000 description 6
125000003277 amino group Chemical group 0.000 description 6
125000004663 dialkyl amino group Chemical group 0.000 description 6
239000011630 iodine Substances 0.000 description 6
229910052740 iodine Inorganic materials 0.000 description 6
238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 6
229910052751 metal Inorganic materials 0.000 description 6
239000002184 metal Substances 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
229910052698 phosphorus Inorganic materials 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 6
NHPBDVZRYPODPF-UHFFFAOYSA-N 2-[(2-cyano-3-methylsulfanylpropoxy)methyl]-3-methylsulfanylpropanenitrile Chemical compound CSCC(C#N)COCC(C#N)CSC NHPBDVZRYPODPF-UHFFFAOYSA-N 0.000 description 5
125000004183 alkoxy alkyl group Chemical group 0.000 description 5
CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 description 5
239000005289 controlled pore glass Substances 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000012071 phase Substances 0.000 description 5
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 5
JBWYRBLDOOOJEU-UHFFFAOYSA-N 1-[chloro-(4-methoxyphenyl)-phenylmethyl]-4-methoxybenzene Chemical compound C1=CC(OC)=CC=C1C(Cl)(C=1C=CC(OC)=CC=1)C1=CC=CC=C1 JBWYRBLDOOOJEU-UHFFFAOYSA-N 0.000 description 4
QWTBDIBOOIAZEF-UHFFFAOYSA-N 3-[chloro-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile Chemical compound CC(C)N(C(C)C)P(Cl)OCCC#N QWTBDIBOOIAZEF-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
239000008351 acetate buffer Substances 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
238000009833 condensation Methods 0.000 description 4
230000005494 condensation Effects 0.000 description 4
238000006482 condensation reaction Methods 0.000 description 4
JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
239000012046 mixed solvent Substances 0.000 description 4
125000004437 phosphorous atom Chemical group 0.000 description 4
238000000746 purification Methods 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
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125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000006384 oligomerization reaction Methods 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000003431 oxalo group Chemical group 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
CCVKPWUMYBYHCD-UHFFFAOYSA-N oxolane;pyridine Chemical compound C1CCOC1.C1=CC=NC=C1 CCVKPWUMYBYHCD-UHFFFAOYSA-N 0.000 description 1
238000005192 partition Methods 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-M periodate Chemical class [O-]I(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-M 0.000 description 1
238000005502 peroxidation Methods 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
YWVYZMVYXAVAKS-UHFFFAOYSA-N pyridin-1-ium;trifluoromethanesulfonate Chemical compound C1=CC=[NH+]C=C1.[O-]S(=O)(=O)C(F)(F)F YWVYZMVYXAVAKS-UHFFFAOYSA-N 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
239000002336 ribonucleotide Substances 0.000 description 1
125000002652 ribonucleotide group Chemical group 0.000 description 1
108091092562 ribozyme Proteins 0.000 description 1
230000002000 scavenging effect Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000002639 sodium chloride Nutrition 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
235000011008 sodium phosphates Nutrition 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
TZGODTCAKVHMFG-UHFFFAOYSA-N sulfanylmethoxymethanethiol Chemical compound SCOCS TZGODTCAKVHMFG-UHFFFAOYSA-N 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
VSQQQLOSPVPRAZ-RRKCRQDMSA-N trifluridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(F)(F)F)=C1 VSQQQLOSPVPRAZ-RRKCRQDMSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
238000000870 ultraviolet spectroscopy Methods 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/11—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same saturated acyclic carbon skeleton
- C07C255/13—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same saturated acyclic carbon skeleton containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/067—Pyrimidine radicals with ribosyl as the saccharide radical
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/167—Purine radicals with ribosyl as the saccharide radical
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Engineering & Computer Science (AREA)
Biotechnology (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Saccharide Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

CA2577922A 2004-08-26 2005-08-25 Compose de phosphoramidite et procede de fabrication d'oligo-arn Expired - Fee Related CA2577922C (fr)

Applications Claiming Priority (7)

Application Number	Priority Date	Filing Date	Title
JP2004-246185		2004-08-26
JP2004246185		2004-08-26
JP2005-110817		2005-04-07
JP2005110817		2005-04-07
JP2005193313		2005-07-01
JP2005-193313		2005-07-01
PCT/JP2005/015420 WO2006022323A1 (fr)	2004-08-26	2005-08-25	Compose de phosphoramidite et procede de fabrication d’oligo-arn

Publications (2)

Publication Number	Publication Date
CA2577922A1 CA2577922A1 (fr)	2006-03-02
CA2577922C true CA2577922C (fr)	2013-06-25

Family

ID=35967530

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2577922A Expired - Fee Related CA2577922C (fr)	2004-08-26	2005-08-25	Compose de phosphoramidite et procede de fabrication d'oligo-arn

Country Status (12)

Country	Link
US (1)	US8691970B2 (fr)
EP (1)	EP1795536B1 (fr)
JP (1)	JP5157168B2 (fr)
KR (1)	KR101281836B1 (fr)
CN (1)	CN101048423B (fr)
AT (1)	ATE556085T1 (fr)
AU (1)	AU2005275801B2 (fr)
BR (1)	BRPI0514644A (fr)
CA (1)	CA2577922C (fr)
ES (1)	ES2386709T3 (fr)
MX (1)	MX2007002245A (fr)
WO (1)	WO2006022323A1 (fr)

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KR102670605B1 (ko)	2018-04-24	2024-05-29	스미또모 가가꾸 가부시끼가이샤	아미다이트 화합물 및 그 화합물을 사용한 폴리뉴클레오티드의 제조 방법
JP7423533B2 (ja)	2018-09-07	2024-01-29	住友化学株式会社	配糖体化合物の製造方法
US12509483B2 (en)	2019-10-11	2025-12-30	Sumitomo Chemical Company, Limited	Method for producing nucleic acid oligomers
EP4047004B1 (fr) *	2019-10-18	2024-03-06	FUJIFILM Wako Pure Chemical Corporation	Activateur de phosphoramidite
EP4049996B1 (fr)	2019-10-23	2026-01-07	Sumitomo Chemical Company, Limited	Composé glycoside, composé amidite, et procédé de production d'un polynucléotide par utilisation desdits composés
US20230312635A1 (en)	2020-01-29	2023-10-05	Sumitomo Chemical Company, Limited	Method for producing nucleic acid oligomer
WO2021153770A1 (fr)	2020-01-29	2021-08-05	Sumitomo Chemical Company, Limited	Procédé de préparation d'oligomère d'acide nucléique
US12522629B2 (en)	2020-03-27	2026-01-13	Sumitomo Chemical Company, Limited	Method for producing nucleic acid oligomer
CN115362163B (zh)	2020-04-14	2025-04-11	住友化学株式会社	核酸寡聚物的制造方法
US20230192755A1 (en)	2020-04-14	2023-06-22	Sumitomo Chemical Company, Limited	Composition containing nucleic acid oligomer
US20230242570A1 (en)	2020-07-09	2023-08-03	Sumitomo Chemical Company, Limited	Method for producing nucleic acid oligomer
JP7719788B2 (ja)	2020-09-24	2025-08-06	住友化学株式会社	核酸オリゴマーの製造方法
KR20240028416A (ko)	2021-07-06	2024-03-05	스미또모 가가꾸 가부시끼가이샤	핵산 올리고머를 함유하는 조성물
KR20240082343A (ko)	2021-09-28	2024-06-10	스미또모 가가꾸 가부시끼가이샤	정제 디클로로아세트산의 제조 방법
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2005
- 2005-08-25 ES ES05780944T patent/ES2386709T3/es not_active Expired - Lifetime
- 2005-08-25 CN CN2005800363733A patent/CN101048423B/zh not_active Expired - Lifetime
- 2005-08-25 CA CA2577922A patent/CA2577922C/fr not_active Expired - Fee Related
- 2005-08-25 BR BRPI0514644-5A patent/BRPI0514644A/pt not_active IP Right Cessation
- 2005-08-25 KR KR1020077006676A patent/KR101281836B1/ko not_active Expired - Lifetime
- 2005-08-25 AT AT05780944T patent/ATE556085T1/de active
- 2005-08-25 JP JP2006531972A patent/JP5157168B2/ja not_active Expired - Lifetime
- 2005-08-25 EP EP05780944A patent/EP1795536B1/fr not_active Expired - Lifetime
- 2005-08-25 WO PCT/JP2005/015420 patent/WO2006022323A1/fr not_active Ceased
- 2005-08-25 AU AU2005275801A patent/AU2005275801B2/en not_active Ceased
- 2005-08-25 MX MX2007002245A patent/MX2007002245A/es active IP Right Grant
- 2005-08-25 US US11/574,308 patent/US8691970B2/en active Active

Also Published As

Publication number	Publication date
JPWO2006022323A1 (ja)	2008-05-08
WO2006022323A1 (fr)	2006-03-02
US20070282097A1 (en)	2007-12-06
AU2005275801A1 (en)	2006-03-02
KR101281836B1 (ko)	2013-07-03
BRPI0514644A (pt)	2008-06-17
CN101048423A (zh)	2007-10-03
EP1795536A1 (fr)	2007-06-13
KR20070054688A (ko)	2007-05-29
JP5157168B2 (ja)	2013-03-06
EP1795536A4 (fr)	2009-04-08
CN101048423B (zh)	2011-06-08
ATE556085T1 (de)	2012-05-15
AU2005275801B2 (en)	2012-05-10
ES2386709T3 (es)	2012-08-27
CA2577922A1 (fr)	2006-03-02
EP1795536B1 (fr)	2012-05-02
MX2007002245A (es)	2007-04-20
AU2005275801A2 (en)	2006-03-02
US8691970B2 (en)	2014-04-08

Legal Events

Date	Code	Title	Description
2010-08-24	EEER	Examination request
2018-10-08	MKLA	Lapsed	Effective date: 20180827

Publication	Publication Date	Title
CA2577922C (fr)	2013-06-25	Compose de phosphoramidite et procede de fabrication d'oligo-arn
EP1995253B1 (fr)	2016-12-21	Procede pour detacher un groupe protecteur d'un acide nucleique
EP2017282A1 (fr)	2009-01-21	Procede de coiffage d'acide oligonucleique
CA2642693A1 (fr)	2007-08-30	Procede de clivage d'un groupe protecteur d'acide nucleique
CA2659703C (fr)	2014-03-11	Procede pour introduire un groupe protecteur d'acide nucleique
RU2415862C2 (ru)	2011-04-10	Производное фосфорамидита и способ получения олиго-рнк